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An Air-liquid Interface Bronchial Epithelial Model for Realistic, Repeated Inhalation Exposure to Airborne Particles for Toxicity Testing
Published on: May 13, 2020
Chitosan nanoparticles are compatible with respiratory epithelial cells in vitro
Ana Grenha1, Christopher I Grainger, Lea Ann Dailey
1University of Santiago de Compostela, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, 15782 Santiago de Compostela, Spain.
Summary
Novel nanoparticle (NP) microspheres show promising biocompatibility for pulmonary drug delivery. These formulations demonstrated no toxicity and maintained cell barrier integrity in vitro, supporting their development for delivering therapeutic macromolecules.
Area of Science:
- Biomaterials science
- Nanotechnology
- Respiratory medicine
Background:
- Pulmonary administration offers targeted delivery of therapeutics.
- Nanoparticle (NP) formulations require biocompatible carriers for safe inhalation.
- Mannitol microspheres are explored as carriers for respirable drug delivery.
Purpose of the Study:
- To assess the in vitro biocompatibility of novel respirable nanoparticle-entrapped mannitol microspheres.
- To evaluate the impact of these formulations on human respiratory epithelial cells.
- To determine the suitability of these microspheres for pulmonary drug delivery.
Main Methods:
- Human respiratory cell lines (Calu-3, A549) were exposed to various NP:mannitol microsphere formulations.
- Cell viability was assessed using the MTT assay.
- Transepithelial electrical resistance (TER) and solute permeability were measured in Calu-3 cell layers.
- Confocal microscopy was used to investigate NP internalisation and mucoadhesion.
Main Results:
- No significant toxicity was observed in Calu-3 or A549 cells at NP concentrations below 1.3 mg/ml for up to 48 hours.
- The NP:mannitol 20:80 formulation did not alter transepithelial electrical resistance or solute permeability in Calu-3 cell layers.
- Confocal microscopy indicated mucoadhesion but no NP internalisation under the tested conditions.
Conclusions:
- The evaluated mannitol microsphere formulations containing nanoparticles exhibit favorable in vitro biocompatibility.
- These findings support the potential of these microspheres for pulmonary administration of therapeutic macromolecules.
- The formulations possess desirable aerodynamic properties and protein encapsulation capacity, alongside demonstrated biocompatibility.
